Kumatakenin alleviates cadmium-induced testicular toxicity by restoring steroidogenesis and suppressing oxido-inflammatory responses.

Abstract

Cadmium (Cd) is a highly toxic compound that induces deleterious effects on living organisms and causes multi-organ toxicity, including testicular damage. Kumatakenin (KMK) is a flavonoid with potential antioxidant and anti-inflammatory properties. The present study was designed to assess the protective effects of KMK against Cd prompted testicular injury in rats. 24 albino rats were divided into four groups including control, Cd (5 mg/kg), Cd + KMK (5 mg/kg + 25 mg/kg) and KMK (25 mg/kg). Following a 56-day trial, the rats were anesthetized, dissected and further analyses were performed. The results showed that Cd caused significant oxidative damage in the testes via increasing ROS and MDA levels and lowering Nrf-2 and HO-1 mRNA expressions and antioxidant enzymes activities. Moreover, Cd increased the expressions of TLR4, MyD88, TRAF6 and NF-κB, which further elevated the levels of inflammatory markers (TNF-α, COX-2, IL-1β and IL-6). Moreover, Cd exposure also resulted in significant upregulation in the mRNA expressions of pro-apoptotic markers (Bax and Caspase-3), while reducing the expressions of anti-apoptotic marker (Bcl-2) as well as steroidogenic markers (StAR, 3β-HSD, and 17β-HSD). Additionally, Cd lowered the levels of plasma testosterone which further caused a reduction in sperm count, and motility while increasing sperm abnormalities. Cd also induced histological disruptions in the testicular tissues. However, KMK treatment mitigated Cd induced disruptions in the testicular tissues. These outcomes demonstrate that KMK has the ability to modulate the mRNA expression of genes associated with the TLR4/NF-κB and Bax/Bcl-2/Caspase-3 pathways, thereby mitigating testicular injury.